Our previous studies have shown that in chemical-transformation, there is a gradual change in the cytogenetic profile. The direction of the change i.e., either toward a stable and a viable karyotype or toward nonstable and inviable karyotype, depends on the extent of the initial damage. Notwithstanding, for example, the myriads of chromosomal aberrations initially induced by MNNG, among the numerous clones isolated, only five karyotypic variants were observed. Additionally, of all the cells analyzed, only two markers were observed. This may suggest that these cells examined for karyology might have been derived from one or two cells. To provide some answers to the question whether or not chromosomal anomalies are the cause or the consequence of carcinogenesis, the following correlative studies are proposed (1) A comparative clastogenicity of N-methyl-N'-nitrosoguanidine (MNNG), adriamycin (ADM) and daunomycin (DM) in a short-term in vitro treatment, using Chinese hamster ovary (CHO) and mouse embryo cells as test materials. (2) In vitro transformation of CHO cells (secondary cell line) and mouse embryo cell lines with MNNG, ADM or DM, coupled with systematic monitoring of the transformed cells for karyotypic changes. (3) Direct tumorigenicity of MNNG, ADM and DM through submuscular or intradermal administration of the test compound, and subsequent cytogenetic analysis of the tumor cells. (4) Indirect tumorigenicity of MNNG, ADM or DM through submuscular or intradermal implantation of transformed cells followed by karyotypic evaluation of tumor cells.